Beta-Blocker Use and Outcomes in Nursing Home Residents with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Beta-blockers improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their role in older nursing home residents with HFrEF. METHODS: From the combined OPTIMIZE-HF and Alabama Heart Failure Project data sets, we assembled a propensity score-matched balanced cohort of 6494 hospitalized patients ≥65 years with HFrEF (ejection fraction ≤40%). In our primary approach, hazard ratios (HRs) and 95% confidence intervals (CI)s for outcomes associated with discharge prescriptions for beta- blockers were estimated, examining for heterogeneity by admission from nursing homes. In our sensitivity approach, we examined these associations in a separately assembled propensity score-matched cohort of 122 patients admitted from nursing homes. RESULTS: In the matched primary cohort of 6494 patients, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.80 (0.74-0.87) and 0.94 (0.86-1.02), respectively. Respective HRs (95% CIs) in the nursing home and non-nursing home subgroups were 0.77 (0.51-1.16) and 0.81 (0.74-0.87) for all-cause mortality (interaction P: 0.653) and 1.06 (0.53-2.12) and 0.89 (0.82-0.96) for heart failure readmission (interaction P: 0.753). In the matched sensitivity cohort of 122 patients admitted from nursing homes, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.86 (0.55-1.35) and 1.07 (0.52-2.22), respectively. Similar associations were observed for 30-day outcomes. CONCLUSIONS: Beta-blocker use was associated with a lower risk of all-cause mortality but not of heart failure readmission in older patients with HFrEF, which were similar for patients admitted and not admitted from nursing homes.

Cardiovascular Disease in Older Women.

Cardiovascular disease is the major cause of death in women. Older women remain at risk for coronary artery disease/cardiovascular disease, but risk-modifying behavior can improve outcomes. Women have a different symptom profile and have been underdiagnosed and undertreated as compared with men. Although older women are underrepresented in trials, clinicians should be more attuned to the prevention, diagnosis, and treatment of cardiovascular disease in older women.

Digoxin Use and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking. METHODS: Of the 11,900 patients with HFrEF (ejection fraction ≤45%) in Medicare-linked OPTIMIZE-HF, 8401 were not on digoxin, of whom 1571 received discharge prescriptions for digoxin. We matched 1531 of these patients with 1531 not receiving digoxin by propensity scores for digoxin use. The matched cohort (n = 3062; mean age, 76 years; 44% women; 14% African American) was balanced on 52 baseline characteristics. We assembled a second matched cohort of 2850 patients after excluding those with estimated glomerular filtration rate <15 mL/min/1.73 m2 and heart rate <60 beats/min. Hazard ratios (HRs) and 95% confidence intervals (CIs) for digoxin-associated outcomes were estimated in the matched cohorts. RESULTS: Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30 days (HR, 0.74; 95% CI, 0.59-0.93), 1 year (HR, 0.81; 95% CI, 0.72-0.92), and 6 years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6 years but not 30 days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission but not all-cause mortality.

Spironolactone and Outcomes in Older Patients with Heart Failure and Reduced Ejection Fraction.

BACKGROUND: The efficacy of mineralocorticoid receptor antagonists or aldosterone antagonists in heart failure with reduced ejection fraction (HFrEF) is well known. Less is known about their effectiveness in real-world older patients with HFrEF. METHODS: Of the 8206 patients with heart failure and ejection fraction ≤35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF registry, 6986 were eligible for spironolactone therapy based on serum creatinine criteria (men ≤2.5 mg/dL, women ≤2.0 mg/dL) and 865 received a discharge prescription for spironolactone. Using propensity scores for spironolactone use, we assembled a matched cohort of 1724 (862 pairs) patients receiving and not receiving spironolactone, balanced on 58 baseline characteristics (Creatinine Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the above process to assemble a secondary matched cohort of 1638 (819 pairs) patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (eGFR Cohort: mean age, 75 years, 42% women, 17% African American). RESULTS: In the matched Creatinine Cohort, spironolactone-associated hazard ratios (95% confidence intervals) for all-cause mortality, heart failure readmission, and combined endpoint of heart failure readmission or all-cause mortality were 0.92 (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87 (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02). CONCLUSIONS: These findings provide evidence of consistent, albeit modest, clinical effectiveness of spironolactone in older patients with HFrEF regardless of renal eligibility criteria used. Additional strategies are needed to improve the effectiveness of aldosterone antagonists in clinical practice.

Palliative care in cardiac transplantation: an evolving model.

It is currently estimated that 5.7 million Americans live with heart failure. Of these, less than 3000 will receive a heart transplant this year, according to the US Department of Health and Human Services Organ Procurement and Transplantation Network. With successful transplantation can come significant emotional and physical symptoms that are not always addressed. Although palliative care is an interdisciplinary subspecialty designed to alleviate multiple domains of suffering in serious illness, many mistakenly associate it solely with the end of life. Traditionally associated with cancer, research into the role of palliative care in other chronic illnesses and complex life-changing therapies such as solid organ transplantation remains scarce but is nonetheless developing. Here, we try to investigate a potential role for palliative care for heart transplant recipients. Early research thus far has demonstrated importance of early involvement of palliative care teams and the significant improvement of physical and emotional symptoms in the pre- and post-transplant period. Nevertheless, more research is warranted to determine the ideal timing of palliative care integration, the effects on health care resource utilization, and whether improving quality of life can affect morbidity and mortality. By understanding these critical elements and others we may be able to develop a model for the role of palliative care for heart transplant patients.

Genomewide molecular and biologic characterization of biomembrane formation adjacent to a methacrylate spacer in the rat femoral segmental defect model.

OBJECTIVES: This study focuses upon the morphologic and molecular features of the layer of cells, termed the "biomembrane," which forms around methacrylate spacers in bone segmental defects. The objective of this research was to assess the biomembrane formed in a novel rodent femoral segmental defect model at 4, 8, and 16 weeks with histologic and molecular studies. METHODS: Following Institutional Animal Care and Use Committee approval, a segmental defect was created in the rat femur and stabilized with the AO LockingRatNail and analyzed at 4, 8, and 16 weeks postsurgery using digital radiologic imaging, morphological and immunohistochemical studies, and genomewide gene expression studies employing microarray analysis. RESULTS: The biomembrane formed around the methacrylate spacer was rich in vasculature, which showed vascular endothelial growth factor immunolocalization. The biomembrane supported development of foci of bone and cartilage within it. Bone morphogenetic protein 2 immunolocalization and gene expression were positive within developing osseous and chondrocyte foci. Microarray analysis showed significant expression of key genes related to bone and cartilage formation and angiogenesis. CONCLUSIONS: This rat bone model was effective in creation of the biomembrane. Bone and cartilage foci were formed within the vascularized biomembrane with associated expression of genes critical for bone and cartilage development/formation and vascularization. The polymethyl methacrylate-induced biomembrane offers an exciting potential solution for segmental defects; the biomembrane, may act as a receptive bed and also serve as a source for mesenchymal stem cells, which could be recruited/directed for the healing process.

Utilization of the AO LockingRatNail in a novel rat femur critical defect model.

BACKGROUND: Our objective was to utilize a commercially available rodent locked intramedullary nail in a rat femur diaphyseal defect. This model is needed for future studies where materials in the critical defect could be modified with agents to fight infection (antibiotics) or promote osteogenesis. METHODS: After unsatisfactory attempts to develop a reliable femur critical size defect model utilizing various forms of fixation, a locked intramedullary nailing system (AO LockingRatNail) was employed in 105 male Sprague Dawley rats. A 5 mm critical size mid-diaphyseal femoral defect was created using a pneumatic sagittal saw. The intramedullary nail was placed in the femur in a retrograde manner. A prefabricated polymethyl-methacrylate (PMMA) spacer was utilized to fill the defect. Once adequate alignment was achieved, two locking pegs were placed (one distal, one proximal) to provide stable fixation. RESULTS: The technique was successful in 90% of femurs (95 of 105). The majority of complications centered on failure of the placement of locking pegs (7 of 10). One rat presented with migration of the nail out of the knee. Two rats presented with fractures not recognized intraoperatively. These complications occurred early in the study and decreased as surgical experience increased. Surgery was tolerated well by the rats as reflected by significant weight postoperative gain (p < .001). CONCLUSIONS: The AO LockingRatNail is a novel, reproducible, and successful method for stabilization of critical size femoral diaphyseal defects in the rat. This model has future value in the examination of the biological processes involved in the healing of critical bone defects.

Osteogenic and chondrogenic potential of biomembrane cells from the PMMA-segmental defect rat model.

A layer of cells (the "biomembrane") has been identified in large segmental defects between bone and surgically placed methacrylate spacers or antibiotic-impregnated cement beads. We hypothesize that this contains a pluripotent stem cell population with potential valuable applications in orthopedic tissue engineering. Objectives using biomembranes harvested from rat segmental defects were to: (1) Culture biomembrane cells in specialized media to direct progenitor cells along bone or cartilage cell differentiation lineages; (2) evaluate harvested biomembranes for mesenchymal stem cell markers, and (3) define relevant gene expression patterns in harvested biomembranes using microarray analysis. Culture in osteogenic media produced mineralized nodules; culture in chondrogenic media produced masses containing chondroitin sulfate/sulfated proteoglycans. Molecular analysis of biomembrane cells versus control periosteum showed significant upregulation of key genes functioning in mesenchymal stem cell differentiation, development, maintenance, and proliferation. Results identified significant upregulation of WNT receptor signaling pathway genes and significant upregulation of BMP signaling pathway genes. Findings confirm that the biomembrane has a pluripotent stem cell population. The ability to heal large bone defects is clinically challenging, and novel tissue engineering uses of the biomembrane hold great promise in treating non-unions, open fractures with large bone loss and/or infections, and defects associated with tumor resection.